Effects of Perfluorinated alkyl substances (PFAS) on amphibian body and liver condition: Is lipid metabolism being perturbed throughout metamorphosis?

<p>Per- and polyfluoroalkyl substances (PFAS) are a widespread class of pollutants and may interact with peroxisome proliferator activated receptors (PPAR), therefore altering lipid homeostasis. Using the model <i>Xenopus laevis,</i> we investigated the effect of PFAS on lipid homeostasis and whether this correlated to changes in scaled mass index (SMI, a measure of body condition) or hepatic condition, (b) gene expression of targets regulated by PPAR in the liver, and (c) the hepatic lipidome. We chronically exposed tadpoles to 0.5 µg/L of either PFOS, a PFHxS, PFOA, PFHxA, a binary mixture of PFOS and PFHxS (0.5 µg/L of each), or a control, from NF stage 52 through metamorphic climax. Growth, development, and survival were generally not affected, but we detected a sex-specific decrease in body condition (measured as Scaled Mass Index, SMI) at NF 66 and in hepatic condition across metamorphic climax for male <i>X. laevis</i> tadpoles exposed to PFOS. We observed a transient downregulation for apolipoprotein-V (<i>apoa5</i>) at NF 62 for tadpoles exposed to PFHxA. We also observed downregulation of acyl-CoA oxidase 1 (<i>acox1), </i>but only for males exposed to PFHxS. We detected PFAS-specific downregulation of structural glycerophospholipids, while semi-quantitative profiling detected upregulation in numerous glycerophospholipids, sphingomyelins, and diglycerides. Overall, our findings indicate that PFAS can induce sex-specific effects that change across larval development and metamorphosis, suggesting the need for longitudinal studies that explicitly consider sex. We demonstrate that PFAS alter lipid metabolism at low, environmentally relevant concentrations, through divergent mechanisms that are not related to PPARs these effects occurred in the absence of major effects on body condition, suggesting, demonstrating the need for more molecular studies to elucidate mechanisms of PFAS-induced lipid dysregulation in amphibians and in other taxa.</p>